The Arrest of Secretion Response

Case Western Reserve University, Cleveland OH

Investigators

Abstract

Recent observations on the "arrest of secretion response" (ASR) in yeast have documented a novel form of intracellular signaling: the protein which initiates the signal, although it is normally at the cell surface, must be trapped within intracellular compartments in order to signal. This project will explore molecular mechanisms which operate along this signaling pathway. In the ASR, inhibition of transport along the secretory path in sec mutants relocates proteins of the nuclear pore complex (NPC), inhibits nuclear import and also relocates nucleoplasmic proteins to the cytoplasm. Protein kinase C (Pkc1p) and two of the transmembrane proteins of the Wsc family are required for these events. They nevertheless do not require the Pkc1p MAP kinase cascade. Moreover, Wsc proteins trapped along the secretory path are required for signaling, as opposed to those which are normally at the plasma membrane. Thus, this work will determine * Whether Pkc1p associates with Wsc proteins and whether such association depends on whether an active ASR is occurring, * Whether diacylglycerol is generated when the secretory path is inhibited, i.e. during the ASR, * Whether a genetic screen can identify signaling intermediates which are required, especially those which function downstream of Pkc1p.